Project Summary/Abstract Alzheimer?s disease and its related dementias (AD/ADRD) account for ~$240M in annual healthcare costs in the USA. Mild cognitive impairment (MCI) is a transitional phase in progression of cognitive aging and is a key risk factor for developing ADRDs in reduced timeframes. It is an ideal stage to monitor early cognitive decline (and its neural markers) to identify older adults at risk for ADRDs. Conventional views of MCI neuropathology are memory/cognitive-centric; it is widely assumed speech-language symptoms are among the last to emerge in the cascade of events during preclinical ADRD. Challenging these views, we have recently documented several key findings that MCI compromises auditory neural processing and the brain?s ability to accurately categorize speech sounds, exposing a new sensory-based pathophysiology of early cognitive decline outside typical memory and executive functioning sequela. We now aim to expand our ongoing brain imaging studies on speech categorization and novel sound learning (R01DC016267) to characterize early neural declines in these fundamental speech functions in older adults with MCI/ADRDs. In preliminary work, we have discovered MCI is associated with hypersensitive cortical brain responses to speech as measured via EEG. These physiological changes occur in tandem with behavioral deficits in rapid speech labeling and are not observed in normal aging adults. Using behavior and neuroimaging (EEG) approaches, we will test the hypothesis that MCI is associated with ?pre-clinical? deficits in auditory-sensory brain processing that manifest in a reduced ability to properly map acoustic signals to the perceptual categories required for speech understanding. Aim 1 will compare speech-evoked EEGs from young, neurotypical listeners to new data collected in older adults with and without clinical diagnosis of MCI/ADRD. Outcomes will establish efficacy of speech-EEG as a new functional biomarker of MCI and resolve whether their perceptual speech deficits are due to impaired auditory- or linguistic-based processing. Comparing MCI vs. AD groups will assess ERP changes that track with disease progression. Aim 2 will compare the new functional (EEG) measures with gold-standard structural indices (MRI volumetrics) to establish direct links between electrophysiological and anatomical biomarkers of MCI/ADRDs. Relevance to Alzheimer?s disease and/or its related dementias: Uncovering MCI-related deficits in the brain?s precise encoding of speech (a listening skill) would be a significant advance which could offer a more sensitive neurodiagnostic for cognitive decline in ADRDs, potentially before the emergence of obvious memory and cognitive problems. Success of these exploratory studies may therefore fuel additional research to fully develop our EEG paradigms into rapid (< 5-10 min), low-cost, and non-invasive diagnostics for early cognitive impairments.